Abstract
Over the last two decades, N-heterocyclic carbene (NHC)–copper catalysts have received considerable attention in organic synthesis. Despite the popularity of copper complexes containing monodentate NHC ligands and recent development of poly(NHC) platforms, their application in C–C and C–heteroatom cross-coupling reactions has been limited. Recently, we reported an air-assisted Sonogashira-type cross-coupling catalyzed by well-defined cationic copper-pincer bis(NHC) complexes. Herein, we report the application of these complexes in Ullmann-type C–X (X = N, O) coupling of azoles and phenols with aryl halides in a relatively short reaction time. In contrast to other well-defined copper(I) catalysts that require an inert atmosphere for an efficient C–X coupling, the employed Cu(I)-pincer bis(NHC) complexes provide good to excellent yields in air. The air-assisted reactivity, unlike that in the Sonogashira reaction, is also affected by the base employed and the reaction time. With Cs2CO3 and K2CO3, the oxygen-generated catalyst is more reactive than the catalyst formed under argon in a short reaction time (12 h). However, the difference in reactivity is compromised after a 24 h reaction with K2CO3. The efficient pincer Cu-NHC/O2/Cs2CO3 system provides great to excellent cross-coupling yields for electronically diverse aryl iodides and imidazole derivatives. The catalyst scope is controlled by a balance between nucleophilicity, coordinating ability, and the steric hindrance of aryl halides and N-/O-nucleophiles.
Highlights
The N-arylazoles and biarylethers are among the most commonly found motifs in pharmaceuticals, biologically active molecules, crop-protection chemicals, and material science
To compare the catalytic activity of the cationic pincer Cu-N-heterocyclic carbene (NHC) complexes to one of the most efficient copper-carbene catalysts known to date, [Cu(IPr)Cl] (4), it was prepared by modifying a published procedure (Santoro et al, 2013; Lazreg et al, 2015)
We chose the coupling of imidazole and 4-iodoacetophenone as a model reaction to determine the optimal conditions for catalysis (Table 1)
Summary
The N-arylazoles and biarylethers are among the most commonly found motifs in pharmaceuticals, biologically active molecules, crop-protection chemicals, and material science. To achieve milder C–N/C– O coupling conditions, efforts have focused on the use of more activated arenes such as arylbismuth (Barton et al, 1988), -tin, (Davydov et al, 2002) -lead (Lopez-Alvarado et al, 1995), silanes (Lam et al, 2000), and -boronic acids (Lam et al, 1998; Mederski et al, 1999; Collot et al, 2000) Some of these methods are limited in scope to certain azole and arenes or produce toxic side-products, e.g., copper-catalyzed N-phenylation of indoles by triphenylbismuth bis(trifluoroacetate) or synthesis of N-arylimidazoles using p-tolyllead triacetate and Cu(OAc) catalyst (Barton et al, 1988; Lopez-Alvarado et al, 1995). The scope has been recently extended to heterocycles and diarylethers (Lam et al, 2001; Guillou et al, 2009; Wentzel et al, 2009; Liu et al, 2010; Wang et al, 2010)
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